Tpe-tfpy: lysosome-specific aiegen fluorescent probe for in-vivo tumor imaging

Overview

TPE-TFPy is a novel aggregation-induced emission luminogen (AIEgen) designed for lysosome-specific fluorescence imaging in both cellular and in-vivo settings. The probe forms nano-sized aggregates in aqueous media due to its high hydrophobicity, and these aggregates are internalized into lysosomes through endocytosis, producing bright, high-contrast fluorescence upon photoexcitation. In tumor-bearing mice using the 4T1 breast cancer model, intratumor injection of TPE-TFPy produced intense fluorescence at the tumor site that persisted for at least 24 hours, demonstrating strong tumor retention. The technology is positioned for eventual translation into PET ligand development for lysosomal protein and glycosaminoglycan imaging.

Technical specifications

• AIE-active fluorophore: TPE-TFPy exhibits aggregation-induced emission, meaning it fluoresces strongly in aggregate form rather than in dilute solution.
• Lysosome selectivity: Confocal laser scanning microscopy in HeLa cells confirmed clear visualization of round and oval-shaped lysosomes with high signal-to-background contrast.
• Endocytosis-mediated uptake: Nano-aggregates formed in culture media are internalized into lysosomes via endocytosis, enabling passive subcellular targeting.
• In-vivo tumor retention: In 4T1 tumor-bearing mice, fluorescence was detectable at the tumor site for at least 24 hours post-injection, indicating strong binding affinity and retention.
• Working concentration: Effective imaging demonstrated at 10⁻⁴ M aqueous solution with 100 μL injection volume.
• Potential extension: Designed with future application as PET ligands targeting lysosomal proteins and glycosaminoglycans.

Technology readiness level

TPE-TFPy has been validated at the preclinical research stage. In-vitro cellular imaging in HeLa cells confirmed lysosome-specific targeting and high-contrast fluorescence. In-vivo validation using the 4T1 breast tumor mouse model demonstrated strong tumor fluorescence and sustained 24-hour retention after intratumor injection. Further validation of binding affinity toward lysosomal proteins and glycosaminoglycans is planned to support translation toward PET ligand applications. The probe is currently suitable for collaborative evaluation and licensing discussions.